Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription
Abstract Introduction Despite the long-observed correlation between H3K9me3, chromatin architecture, and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Result Here, we develop EpiGo (Epigenetic perturba...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Genome Biology |
| Online Access: | https://doi.org/10.1186/s13059-020-02201-1 |
| _version_ | 1831674201861259264 |
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| author | Ying Feng Yao Wang Xiangnan Wang Xiaohui He Chen Yang Ardalan Naseri Thoru Pederson Jing Zheng Shaojie Zhang Xiao Xiao Wei Xie Hanhui Ma |
| author_facet | Ying Feng Yao Wang Xiangnan Wang Xiaohui He Chen Yang Ardalan Naseri Thoru Pederson Jing Zheng Shaojie Zhang Xiao Xiao Wei Xie Hanhui Ma |
| author_sort | Ying Feng |
| collection | DOAJ |
| description | Abstract Introduction Despite the long-observed correlation between H3K9me3, chromatin architecture, and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Result Here, we develop EpiGo (Epigenetic perturbation induced Genome organization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to induce genomic clustering and de novo heterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB-induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread in inactive regions but is largely restricted from transcriptional initiation sites in active regions. Finally, Hi-C analysis showed that EpiGo-KRAB reshapes existing compartments mainly at compartment boundaries. Conclusions These results reveal the role of H3K9me3 in genome organization could be partially separated from its function in gene repression. |
| first_indexed | 2024-12-20T03:41:01Z |
| format | Article |
| id | doaj.art-0f0e8451da42416fa2e9117869a58941 |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-12-20T03:41:01Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-0f0e8451da42416fa2e9117869a589412022-12-21T19:54:44ZengBMCGenome Biology1474-760X2020-12-0121112410.1186/s13059-020-02201-1Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcriptionYing Feng0Yao Wang1Xiangnan Wang2Xiaohui He3Chen Yang4Ardalan Naseri5Thoru Pederson6Jing Zheng7Shaojie Zhang8Xiao Xiao9Wei Xie10Hanhui Ma11School of Biotechnology, East China University of Science and Technology, Shanghai, China; School of Life Science and Technology, ShanghaiTech University,Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua UniversitySchool of Life Science and Technology, ShanghaiTech University,School of Life Science and Technology, ShanghaiTech University,School of Pharmacy, East China University of Science and TechnologyDepartment of Computer Science, University of Central FloridaDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical SchoolSchool of Pharmacy, East China University of Science and TechnologyDepartment of Computer Science, University of Central FloridaSchool of Biotechnology, East China University of Science and Technology,Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua UniversitySchool of Life Science and Technology, ShanghaiTech University,Abstract Introduction Despite the long-observed correlation between H3K9me3, chromatin architecture, and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Result Here, we develop EpiGo (Epigenetic perturbation induced Genome organization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to induce genomic clustering and de novo heterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB-induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread in inactive regions but is largely restricted from transcriptional initiation sites in active regions. Finally, Hi-C analysis showed that EpiGo-KRAB reshapes existing compartments mainly at compartment boundaries. Conclusions These results reveal the role of H3K9me3 in genome organization could be partially separated from its function in gene repression.https://doi.org/10.1186/s13059-020-02201-1 |
| spellingShingle | Ying Feng Yao Wang Xiangnan Wang Xiaohui He Chen Yang Ardalan Naseri Thoru Pederson Jing Zheng Shaojie Zhang Xiao Xiao Wei Xie Hanhui Ma Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription Genome Biology |
| title | Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription |
| title_full | Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription |
| title_fullStr | Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription |
| title_full_unstemmed | Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription |
| title_short | Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription |
| title_sort | simultaneous epigenetic perturbation and genome imaging reveal distinct roles of h3k9me3 in chromatin architecture and transcription |
| url | https://doi.org/10.1186/s13059-020-02201-1 |
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